Can COVID-19 gastrointestinal symptoms improve prognosis?

Inpatient COVID-19 patients with gastrointestinal symptoms appear to have reduced pro-inflammatory reactions and mortality, suggesting that the gastrointestinal tract may reduce SARS-CoV-2 inflammation The researchers reported that.

According to Icahn’s Saurabh Mehandru, MD, in a three-cohort international study, SARS-CoV-2 was detected in small intestinal epithelial cells by immunofluorescence staining or electron microscopy in 14 of 16 patients in the final analysis of biopsy patients. it was done. Mount Sinai School of Medicine, New York City, and colleagues.

High-dimensional analysis of GI tissue in COVID-19 patients reveals low levels of inflammation, including down-regulation of major inflammatory genes such as IFNG, CXCL8, CXCL2, IL1B, and reduced frequency of pro-inflammatory dendritic cells became. Control.The infected enterocytes were primarily goblet cells, they said. Gastroenterology..

The findings show that gastrointestinal symptoms, especially the presence of diarrhea, are higher viral load, more serious illness, and Worse result In COVID-19 patients. The abundance of angiotensin converting enzyme 2 (ACE 2) receptors in the epithelial cells of the gastrointestinal tract is thought to promote viral invasion.

Details of the study

In part of the study, Mehandru’s group included 19 COVID-19 patients admitted between April 1, 2020 and April 15, 2020, and intestinal biopsy tissue from 10 uninfected controls. Investigated using immunofluorescence microscopy, CyTOF analysis, and RNA sequencing. .. Patients also underwent procedures such as esophagogastric duodenal endoscopy, colonoscopy, or both.

They also found in two independent cohorts of inpatients (634 in the US and 287 in Europe), disease severity and mortality in patients with and without GI symptoms analyzed by multivariate logistic regression. I checked the rate. The authors said that cases and controls of COVID-19 in the biopsy cohort were comparable for age, gender, hospitalization rate, and associated comorbidities.

Consistent with histological findings, they have disease severity and mortality in patients with GI symptoms, regardless of gender, age, and comorbidities, despite similar nasopharyngeal SARS-CoV-2 viral load. Reported a significant decrease in. In addition, GI-affected COVID-19 patients had reduced levels of major circulatory inflammatory cytokines.

“We need to further investigate the potential role of the gastrointestinal tract in attenuating SARS-CoV-2-related inflammation,” the authors added, adding that the findings were unexpected in light of the potent intestinal expression of ACE2. It was.

They say that one of the possible reasons SARS-CoV-2 induced less severe inflammation in the gut could be the induction of potent neutralizing immunoglobulin A antibodies that are produced primarily in the gut but not. Suggested that there is sex. Fix complement It differs from immunoglobulin G antibodies, which are mainly induced in the lungs.

“I was surprised that the patient who first reported gastrointestinal symptoms such as diarrhea seemed to be much better. I can only guess why,” Mhandler said in a news release. “It is possible that the virus migrated to the gastrointestinal tract and was neutralized by significant enzymatic activity in the intestinal tract or the presence of IgA immunoglobulin, resulting in failure to release the degree of inflammation sometimes seen in the lungs.”

Admitting that the results differ from the results of other reports, suggesting an increase Severity of COVID-19 In the presence of gastrointestinal symptoms, the authors stated that previous associations with worse outcomes were likely due to the inclusion of abnormal liver function tests that could correlate with adverse outcomes.

Still similar data came from 2020 Case control study Of the 278 patients at Columbia University Hospital in New York City, Mehandru said Today’s MedPage. “In patients with COVID-19 with gastrointestinal symptoms (diarrhea, nausea, vomiting), ICU admission rates tended to decline and mortality during short-term follow-up tended to decline significantly.” He said.

Mehandru et al. Revealed dynamic remodeling of GI tissue by SARS-CoV-2, with significant downregulation of pathways associated with inflammation and antigen presentation, especially in the lamina propria, and associated antiviral response. He said he revealed activation of signaling genes. Epithelial compartment.

“In summary, our data detail the previously unassessed response of gastrointestinal tissue to SARS-CoV-2 and understand the potential attenuation of SARS-CoV-2 pathogenicity by the intestinal environment. It provides a rationale for future mechanistic studies to do so, “they wrote.

“Looking forward, our research points out that we need to better understand how intestinal infections are associated with long-term COVID symptoms and the emergence of viral variants. Needs further investigation, “Mehandru said.

The limits of the study included performing gastrointestinal biopsies in patients undergoing clinically indicated procedures, not all of which were in the acute phase of the disease. Also, the authors could not compare patients with and without these symptoms, as only three patients in the biopsy cohort showed GI symptoms. Finally, the infectious virus could not be isolated from the intestinal biopsy, probably due to culture methods, low multiplicity of infection, or inactivation of the virus after contact with intestinal secretions.

“Major confirmation required”

Hashem B at Baylor College of Medicine in Houston. El-Serag, MD, and MPH drew attention to the interpretation of the study. “Generally there are interesting questions, but we have to start over, like a million times,” said El-Serag, who was not involved in the study.

He cited several methodological issues, including a small number of biopsy patients. An unknown reason to scoping them. This may have introduced a selection bias. And the unknown stage of their illness.

“Did the symptoms occur before, during, or during hospitalization because the symptoms were not captured symptomatically or quantitatively,” El-Serag said. “Something, including medication, could have caused gastrointestinal symptoms. Was it a bystander effect, colonization, or a real infection?”

El-Serag added that the study was conducted in three different populations and that the virus was not isolated from the intestine. He said that more rigorous symptom capture and more bowel examinations could lead to more generalizability.

“This is a good hypothesis-generating study, but it needs a lot of confirmation,” he said.

Last updated: March 4, 2021